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Sökning: id:"swepub:oai:DiVA.org:liu-198668" > L-arginine metaboli...

L-arginine metabolism inhibits arthritis and inflammatory bone loss

Cao, Shan (författare)
Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany; Univ Klinikum Erlangen, Germany; Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany; Shanghai Jiao Tong Univ, Peoples R China
Li, Yixuan (författare)
Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany; Univ Klinikum Erlangen, Germany; Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany; Shanghai Jiao Tong Univ, Peoples R China
Song, Rui (författare)
Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany; Univ Klinikum Erlangen, Germany; Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany; Shanghai Jiao Tong Univ, Peoples R China
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Meng, Xianyi (författare)
Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany; Univ Klinikum Erlangen, Germany; Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany
Fuchs, Maximilian (författare)
Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany; Fraunhofer Inst Toxicol & Expt Med, Germany
Liang, Chunguang (författare)
Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany; Univ Wurzburg Hubland, Germany
Kachler, Katerina (författare)
Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany; Univ Klinikum Erlangen, Germany; Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany
Meng, Xinyu (författare)
Shanghai Jiao Tong Univ, Peoples R China
Wen, Jinming (författare)
Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany; Univ Klinikum Erlangen, Germany; Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany; Sun Yat sen Univ, Peoples R China
Schloetzer-Schrehardt, Ursula (författare)
Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany
Taudte, Verena (författare)
Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany; Philipps Univ Marburg, Germany
Gessner, Arne (författare)
Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany
Kunz, Meik (författare)
Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany; Fraunhofer Inst Toxicol & Expt Med, Germany
Schleicher, Ulrike (författare)
Univ Klinikum Erlangen, Germany; Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany
Zaiss, Mario M. (författare)
Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany; Univ Klinikum Erlangen, Germany; Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany
Kastbom, Alf (författare)
Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland
Chen, Xiaoxiang (författare)
Shanghai Jiao Tong Univ, Peoples R China
Schett, Georg (författare)
Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany; Univ Klinikum Erlangen, Germany; Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany
Bozec, Aline (författare)
Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany; Univ Klinikum Erlangen, Germany; Friedrich Alexander Univ FAU Erlangen Nurnberg, Germany
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 (creator_code:org_t)
BMJ PUBLISHING GROUP, 2024
2024
Engelska.
Ingår i: Annals of the Rheumatic Diseases. - : BMJ PUBLISHING GROUP. - 0003-4967 .- 1468-2060. ; 83, s. 72-87
Relaterad länk:
https://doi.org/10.1...
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https://liu.diva-por... (primary) (Raw object)
https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • ObjectivesTo investigate the effect of the L-arginine metabolism on arthritis and inflammation-mediated bone loss.MethodsL-arginine was applied to three arthritis models (collagen-induced arthritis, serum-induced arthritis and human TNF transgenic mice). Inflammation was assessed clinically and histologically, while bone changes were quantified by mu CT and histomorphometry. In vitro, effects of L-arginine on osteoclast differentiation were analysed by RNA-seq and mass spectrometry (MS). Seahorse, Single Cell ENergetIc metabolism by profilIng Translation inHibition and transmission electron microscopy were used for detecting metabolic changes in osteoclasts. Moreover, arginine-associated metabolites were measured in the serum of rheumatoid arthritis (RA) and pre-RA patients.ResultsL-arginine inhibited arthritis and bone loss in all three models and directly blocked TNF alpha-induced murine and human osteoclastogenesis. RNA-seq and MS analyses indicated that L-arginine switched glycolysis to oxidative phosphorylation in inflammatory osteoclasts leading to increased ATP production, purine metabolism and elevated inosine and hypoxanthine levels. Adenosine deaminase inhibitors blocking inosine and hypoxanthine production abolished the inhibition of L-arginine on osteoclastogenesis in vitro and in vivo. Altered arginine levels were also found in RA and pre-RA patients.ConclusionOur study demonstrated that L-arginine ameliorates arthritis and bone erosion through metabolic reprogramming and perturbation of purine metabolism in osteoclasts.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)

Nyckelord

Inflammation; Arthritis; Osteoporosis

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